摘要：SummaryThe efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.Graphical AbstractDisplay OmittedHighlights•HIV vaccine candidate protects against SIVmac251acquisition•V1 deleted envelope immunogens with V2 in α-helical conformation are protective•V2-specific ADCC as correlate of risk•Anti-V1 antibodies interfere with V2-specific ADCCImmunology; molecular structure; virology
